Irreversible Cell Injury and Cell Death Flashcards
The cellular response to injury depends on?
- The type of cell
- The severity
- The duration
Susceptibility of cells to Hypoxia
‣ High
• Neurons: (3-5 min)
‣ Intermediate
• Myocardium, hepatocytes, renal epithelium (30 min - 2 hr)
‣ Low
• Fibroblasts, epidermis, skeletal muscle (many hrs)
What happens in the case of severe and persistent injury?
Severe and persistent injury —> point of no return.
- Inability to reverse mitochondrial dysfunction
- Severe dysfunction of cell membranes (Lysosomal membranes → Lysosomal enzymes)
- Increased intracellular calcium levels
What can necrosis lead to?
• Necrosis —> Pathological (point of no return) —> Oncotic necrosis (oncosis [derived from onkos, meaning swelling).
What does apoptosis lead to?
Physiologic cell death/Programmed cell death.
Name and explain three situations in which the body has reached the point of no return?
◦ Ultrastructural
‣ Swelling
‣ Rupture of plasma membrane and organelles (leakage of contents)
‣ Rupture of nucleus
‣ Mitochondria are swollen and develop amorphous densities
◦ Microscopic
‣ Hypereosinophilic cytoplasm (due to denatured proteins and loss of ribosomes)
‣ Nuclear changes:
‣ Pyknosis (nuclear condensation with shrinkage and intense basophilia)
‣ Karyorrhexis (nuclear fragmentation)
‣ Karyolysis (nuclear dissolution or loss)
◦ Gross (macroscopic)
‣ In general:
• Swelling and pallor (soon after cell death)
• Loss of structural detail and demarcation from adjacent viable tissue
• Discolored (usually white)
• Soft
‣ It varies a lot; it depends of: tissue involved, the nature of the injurious agent, and the time elapsed after cell death.
‣ Necrosis has been classified as coagulative, caseous, liquefactive or lytic, and gangrenous
Microscopic images here
What are the types of oncotic necrosis?
- Coagulative necrosis
- Caseous necrosis
- Liquefactive necrosis
- Gangrenous necrosis
- Fat necrosis
- Necrosis of epithelium
- Sequelae to oncotic necrosis
- Cell death by apoptosis
What is Coagulative necrosis typically caused by?
Hypoxia, ischemia, or toxic injury
Coagulative necrosis image + description
Caseous necrosis image here + description
Liquefactive necrosis image + description
Gangrenous necrosis image (wet) + description
Gangrenous necrosis image + description
What are the three types of fat necrosis?
• Enzymatic:
◦ Occurs secondary to leakage of pancreatic enzymes (lipases) in cases of pancreatitis
• Traumatic:
◦ Blunt trauma or chronic pressure against bony prominences (subcutaneous adipose tissue in recumbent animals)
• Idiopathic (unknown cause): ◦ Necrosis of abdominal fat in overconditioned cattle
Enzymatic fat necrosis
Idiopathic fat necrosis image here
Necrosis of epithelium can occur in?
Any epithelial surface
What are the two types of necrosis epithelium?
- Erosion: Superficial sloughing or exfoliation of dead cells (without rupture of basement membrane)
- Ulcer: Full-thickness necrosis of the epithelium (with rupture of basement membrane)
What does sequelae to Oncotic necrosis elicit?
An inflammatory reaction
What happens as a result of sequelae oncotic necrosis?
- Formation of a sequestrum (foreign material and bone fragments)
- Inflammation with regeneration
- Inflammation with scar formation
Sequelae to oncotic necrosis image
What is physiologic apoptosis?
◦ Programmed cell destruction during embryogenesis
◦ Involution of organs or tissues deprived of hormonal stimulation (endometrial and uterine involution)
◦ Cell deletion in proliferating cell populations (to keep homeostasis). Epithelial cells of the skin, gut, etc..
What causes pathological apoptosis?
Injury from toxins, ROS
What happens as a result of pathological apoptosis?
◦ Mitochondria and DNA damage (radiation, anticancer drugs)
◦ Mediated by cytotoxic T lymphocytes and NK cells
◦ Nutrient deprivation
What is pathological apoptosis regulated by?
◦ *** regulated by pro-apoptic and anti-apoptotic intracellular proteins*** **** that activate gene and enzymes leading to cell death****
What is the purpose of pathological apoptosis?
***Purpose: Eliminates unwanted, potentially harmful, useless, damaged cells***
What is pathological apoptosis morphological characterized by?
Condensation and shrinkage of the cell
What does sequelae to Oncotic necrosis elicit?
An inflammatory reaction
Necrosis of epithelium can occur in?
Any epithelial surface
